研究成果報告書
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1 peroxynitrite angiotensin II ETA MEK/ERK pathway endothelin-1 EDHF (EDHF) EDHF EDHF EDHF
2 2 [phosphodiesterase 3 (PDE3) cilostazol metformin thromboxane A2 ozagrel eicosapentaenoic acid (EPA) angiotensin losartan pioglitazone] EDHF (ACh) EDHF endothelin-1 (ET-1) western blot [ NO ET-1 angiotensin II (Ang II) ] (1) peroxynitrite sarco/endoplasmic reticulum calcium ATPase (2) (STZ) NOSOD NAD(P)H oxidase AP-1 ET-1 (3) 2(OLETF) NAD(P)H oxidase NO 1 2 A. B.C. gp91phox [NAD(P)H oxidase component] (4) 2(OLETF) [ (EDCF, prostanoids)(edhf)] prostanoid cyclooxygenase (COX)-1, AChA. OLETF AChB indomethacin (COX) C. NO D. EDHFOLETF
3 3 COX OLETFCOX (5) STZ ET-1 ET-1 Ang II ETA receptor MEK/ERK pathway (6) 2 GK ET-1 endothelin upregulation, MEK/ERK pathway (7) 2 OLETF (EDHF EDCF ) (4) Cilostazol (EDCF camp/pka pathway EDHF ) Metformin [EDCF ( prostanoids)edhf ]EDCF A2 (ozagrel) EDHF EPA [EDCF EDHF ERK NF-kappaB COX2 ] EDHF 4 2(OLETF) metformin A. B. EDHF C. NO D. COX E. EDCF Metformin EDHF EDCF (4) Ang II ET-1 2 EDHF PDE3 metformin ozagrel EPA EDHF EDCF EDHF
4 14 Takenouchi Y, Kobayashi T, Matsumoto T, Kamata K. Gender differences in age-related endothelial function in the murine aorta. Atherosclerosis Mar 19 [Epub ahead of print] in press. Matsumoto T, Ishida K, Nakayam N, Kobayashi T, Kamata K. Involvement of NO and MEK/ERK pathway in enhancement of endothelin-1-induced mesenteric artery contraction in later-stage type 2 diabetic Goto-Kakizaki rat. Am J Physiol Heart Circ Physiol Mar 13 [Epub ahead of pring] in press. Matsumoto T, Takaoka E, Ishida K, Nakayama N, Noguchi E, Kobayashi T, Kamata K. Abnormalities of endothelium-dependent responses in mesenteric arteries from Otsuka Long-Evans Tokushima Fatty (OLETF) rats are improved by chronic treatment with thromboxane A(2) synthase inhibitor. Atherosclesosis Nov 25. [Epub ahead of print] in press. Matsumoto T, Nakayama N, Ishida K, Kobayashi T, Kamata K. Eicosapentaenoic acid improves imbalance between vasodilator and vasoconstrictor actions of endothelium-derived factors in mesenteric arteries from acts at chronic stage of type 2 diabetes. J Pharmacol Exp Ther. 329: , Takenouchi Y, Kobayashi T, Matsumoto T, Kamata K. Possible involvement of Akt activity in endothelial dysfunction in type 2 diabetic mice. J Pharmacol Sci. 106: , Matsumoto T, Kakami M, Kobayashi T, Kamata K. Gender differences in vascular reactivity to endothelin-1 (1-31) in mesenteric arteries from diabetic mice. Peptides. 29: , Matsumoto T, Noguchi E, Ishida K, Kobayashi T, Yamada N, Kamata K. Metformin normalizes endothelial function by suppressing vasoconstrictor prostanoids in mesenteric arteries from OLETF rats, a model of type 2 diabetes. Am J Physiol Heart Circ Physiol. 295:H1165-H1176, Matsumoto T, Noghichi E, Ishida K, Nakayama N, Kobayashi T, Kamata K. Cilostazol improves endothelial dysfunction by increasing endothelium-derived hyperpolarizing factor response in mesenteric arteries from Type 2 diabetic rats. Eur J Pharmacol. 599: , Kobayashi T, Nogami T, Taguchi K, Matsumoto T, Kamata K. Diabetic state, high plasma insulin and angiotensin II combine to augment endothelin-1-induced vasoconstriction via ETA receptors and ERK. Br J Pharmacol. 155: , Kamata K, Ozawa Y, Kobayashi T, Matsumoto T. Effect of long-term streptozotocin-induced diabetes on coronary vasoconstriction in isolated perfused rat heart. J Smooth Muscle Res. 44: , Matsumoto T, Kakami M, Noguchi E, Kobayashi T, Kamata K. Imbalance between endothelium-derived relaxing and contracting factors in mesenteric arteries from aged OLETF rats, a model of Type 2 diabetes. Am J Physiol Heart Circ Physiol. 293:H1480-H1490, Kobayashi T, Taguchi K, Takenouchi Y, Matsumoto T, Kamata K. Insulin-induced impairment via peroxynitrite production of endothelium-dependent relaxation and sarco/endoplasmic reticulum Ca(2+)-ATPase function in aortas from diabetic rats. Free Radic Biol Med. 43: , Matsumoto T, Kobayashi T, Wachi H, Seyama Y, Kamata K. Vascular NAD(P)H oxidase mediates endothelial dysfunction in basilar arteries from Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Atherosclerosis. 192:15-24, Matsumoto T, Noguchi E, Kobayashi T, Kamata K. Mechanisms underlying the chronic pioglitazone treatment-induced improvement in the impaired endothelium-dependent relaxation seen in aortas from diabetic rats. Free Radic Biol Med. 42: ,
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